Kinases play critical roles in signaling pathways controlling fundamental cellular processes such as proliferation, differentiation, and death (apoptosis). The IL2-inducible T-cell kinase (ITK) is a member of the Tec family of kinases. ITK dysfunction (e.g., overexpression) has been implicated in lung inflammation, recruitment of eosinophils, production of mucus (see Mueller, et al., Attenuation of immunological symptoms of allergic asthma in mice lacking the tyrosine kinase ITK, Journal of Immunology, 170:5056-5063) as well as reduced airway hyperresponsiveness (see Ferrara, et al., Reduced airway hyperresponsiveness and tracheal responses during allergic asthma in mice lacking tyrosine kinase inducible T-cell kinase, Journal of Allergy and Clinical Immunology, 117:780-786). In addition, using knock-out mice, RNAi and chemical inhibitors, ITK has been implicated in T cell-driven inflammatory diseases of the skin (see von Bonin et al. Inhibition of the IL-2-inducible tyrosine kinase (Itk) activity: a new concept for the therapy of inflammatory skin diseases, Exp Dermatol, 20:41-47, 2010). Itk was found to be expressed in lymphoid tissue and upregulated in lesional skin from patients with allergic dermatitis, atopic dermatitis and psoriasis. Itk also plays a role in the pathophysiology of T cell malignancies (see Guo W. et. al., Molecular characteristics of CTA056, a novel Itk inhibitor which selectively targets malignant T cell and modulates oncomirs, Molecular Pharmacology, doi:10.1124/mol.112.079889).
Thus, there is a need for compounds that inhibit the activity of Itk. The present disclosure can fulfill this and related needs.